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The Bristol Radiocarbon Accelerator Mass Spectrometry (BRAMS) Facility was established at the University of Bristol after the commissioning of our dedicated sample preparation laboratories and the installation and acceptance of the BrisMICADAS AMS in 2016. Routine measurements commenced in mid-2016, once validation was completed for each sample type. Herein, we give an overview of the standard pretreatment methods currently employed in the Facility and the results of radiocarbon (14C) determinations on a wide range of standards, blank materials, and intercomparison samples which have been measured during our extensive pretreatment method validation program and during our routine 14C analyses.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
At the centre of the Parkes 64—m radio telescope a region of diameter 17 m has recently been resurfaced to improve its efficiency at high frequencies. The first measurements using this section have been made at 22 GHz, in observations of both continuum sources and water tfapour masers. For these observations the receiver front-end used a mixer cooled in liquid nitrogen, followed by a 5 GHz cryogenic parametric amplifier as a second stage. The option of switching against an offset horn was available and the total system
noise temperature was ∽ 750 K.
The results of 1959-1960 radar measurements of the distance of the Moon are given. The method of reduction of the data is described The possible effects of lunar topography and errors of other origins are discussed, as well as the effects of different constants such as the radii of the Earth and of the Moon.
An experimental study incorporating the use of the Background-Oriented Schlieren (BOS) technique was performed to measure the density field of a rectangular supersonic jet. This technique is easier to set up than conventional schlieren since the optical alignment involving the various mirrors, lenses and knife-edge is replaced by a background pattern and a single digital camera. The acquired images which contain information of density gradients in the flow are solved as a Poisson equation and further processed using deconvolution and tomographic algorithms to generate a 3D domain which contains information about the actual density. 2D slices can then be extracted to quantitatively visualise the density along any required planes. The results from supersonic axisymmetric jets are used for validation of the code; these show excellent agreement with pre-validated CFD data. The results for a rectangular supersonic jet are then obtained. These show good agreement with the CFD data, in terms of shock-cell spacing and overall structure of the jet. The technique has proved useful for investigating axis-switching, a phenomenon generally associated with non-axisymmetric jets.
Neurological soft signs (NSS) have been inconsistently reported in obsessive-compulsive disorder (OCD) but may make an impact on treatment response.
The current study examined the presence of NSS in two independent European samples of OCD patients (combined 85 patients and 88 matched healthy controls) using a standardized instrument and conducted a meta-analysis of all published studies identified in the literature with the aim to provide a more definitive answer to the question of whether OCD patients are characterized by increased NSS.
Both empirical studies found elevated NSS scores in patients compared with matched controls. The results of the meta-analysis, which included 15 studies (combined 498 patients and 520 controls) showed large effect sizes (Hedges' g=1.27, 95% confidence interval 0.80–1.75), indicating that OCD patients have significantly higher rates of NSS than matched controls on both sides of the body and in multiple domains (motor coordination, sensory integration and primitive reflexes). The results were robust and remained largely unchanged in our reliability analyses, which controlled for possible outliers. Meta-regression was employed to examine the role of potential variables of interest including sociodemographic variables, symptom severity, medication effects and the use of different instruments, but none of these variables was clearly associated with NSS.
As a group, OCD patients are characterized by increased rates of NSS, compared with healthy controls. However, their origins and potential clinical importance remain to be clarified. Future directions for research are discussed.
Experts have proposed removing obsessive–compulsive disorder (OCD) from the anxiety disorders section and grouping it with putatively related conditions in DSM-5. The current study uses co-morbidity and familiality data to inform these issues.
Case family data from the OCD Collaborative Genetics Study (382 OCD-affected probands and 974 of their first-degree relatives) were compared with control family data from the Johns Hopkins OCD Family Study (73 non-OCD-affected probands and 233 of their first-degree relatives).
Anxiety disorders (especially agoraphobia and generalized anxiety disorder), cluster C personality disorders (especially obsessive–compulsive and avoidant), tic disorders, somatoform disorders (hypochondriasis and body dysmorphic disorder), grooming disorders (especially trichotillomania and pathological skin picking) and mood disorders (especially unipolar depressive disorders) were more common in case than control probands; however, the prevalences of eating disorders (anorexia and bulimia nervosa), other impulse-control disorders (pathological gambling, pyromania, kleptomania) and substance dependence (alcohol or drug) did not differ between the groups. The same general pattern was evident in relatives of case versus control probands. Results in relatives did not differ markedly when adjusted for demographic variables and proband diagnosis of the same disorder, though the strength of associations was lower when adjusted for OCD in relatives. Nevertheless, several anxiety, depressive and putative OCD-related conditions remained significantly more common in case than control relatives when adjusting for all of these variables simultaneously.
On the basis of co-morbidity and familiality, OCD appears related both to anxiety disorders and to some conditions currently classified in other sections of DSM-IV.
Polypeptide sequences have an inherent tendency to self-assemble into filamentous nanostructures commonly known as amyloid fibrils. Such self-assembly is used in nature to generate a variety of functional materials ranging from protective coatings in bacteria to catalytic scaffolds in mammals. The aberrant self-assembly of misfolded peptides and proteins is also, however, implicated in a range of disease states including neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. It is increasingly evident that the intrinsic material properties of these structures are crucial for understanding the thermodynamics and kinetics of the pathological deposition of proteins, particularly as the mechanical fragmentation of aggregates enhances the rate of protein deposition by exposing new fibril ends which can promote further growth. We discuss here recent advances in physical techniques that are able to characterise the hierarchical self-assembly of misfolded protein molecules and define their properties.
The sequence of 165 nucleotides at the 3´ end of the 1D (VP1) gene of foot-and-mouth disease (FMD) virus was determined for 44 type Asia 1 strains isolated from throughout Asia between 1954–92. Analysis of the relationships between the virus genomes showed epidemiological links not previously evident. The possible origin of the only outbreak of FMD Asia 1 to have occurred in Europe, in Greece in 1984, was identified because the nucleotide sequence of this virus was closely-related to the sequences of those present in the Middle East between 1983–5.
Variation in the region sequenced was not as great as that seen in the other FMDV serotypes and all viruses shared greater than 85% nucleotide identity. Thus all the virus isolates examined were considered to belong to a single genotype.
A database of Asia 1 virus sequences has been established which will facilitate the rapid analysis of new outbreaks strains.
Obsessive–compulsive disorder (OCD) is probably an etiologically heterogeneous condition. Many patients manifest other psychiatric syndromes. This study investigated the relationship between OCD and co-morbid conditions to identify subtypes.
Seven hundred and six individuals with OCD were assessed in the OCD Collaborative Genetics Study (OCGS). Multi-level latent class analysis was conducted based on the presence of eight co-morbid psychiatric conditions [generalized anxiety disorder (GAD), major depression, panic disorder (PD), separation anxiety disorder (SAD), tics, mania, somatization disorders (Som) and grooming disorders (GrD)]. The relationship of the derived classes to specific clinical characteristics was investigated.
Two and three classes of OCD syndromes emerge from the analyses. The two-class solution describes lesser and greater co-morbidity classes and the more descriptive three-class solution is characterized by: (1) an OCD simplex class, in which major depressive disorder (MDD) is the most frequent additional disorder; (2) an OCD co-morbid tic-related class, in which tics are prominent and affective syndromes are considerably rarer; and (3) an OCD co-morbid affective-related class in which PD and affective syndromes are highly represented. The OCD co-morbid tic-related class is predominantly male and characterized by high conscientiousness. The OCD co-morbid affective-related class is predominantly female, has a young age at onset, obsessive–compulsive personality disorder (OCPD) features, high scores on the ‘taboo’ factor of OCD symptoms, and low conscientiousness.
OCD can be classified into three classes based on co-morbidity. Membership within a class is differentially associated with other clinical characteristics. These classes, if replicated, should have important implications for research and clinical endeavors.
This report, which was sponsored by the Life Board of the Faculty and Institute of Actuaries, was originally published in November 1997.
Because it is referred to several times in the paper ‘Reserving, Pricing and Hedging for Policies with Guaranteed Annuity Options’, and in the discussions of the paper, and because it is not easily accessible elsewhere, it is printed here as a background paper for reference.
We investigated primary human herpesvirus-6 and -7 (HHV-6, HHV-7) infections as a cause of rashes incorrectly diagnosed as measles in Brazilian children. Sera from 124 patients, aged 4 months to 17 years, from the states of Rio de Janeiro and Espírito Santo, in whom measles, rubella and parvovirus B19 infections had been excluded, were studied using indirect immunofluorescence antibody avidity tests; 38 (31%) had evidence of primary HHV-6 and/or HHV-7 infections. Twenty four children had primary HHV-6 infection, either recent or coincident with the rash, and similarly 31 had primary HHV-7 infection. Remarkably, almost half (17) of primary infections were dual HHV-6 and HHV-7 infections with the majority, 12 (71%), in children less than 1 year old. HHV-7 infection occurred earlier than previously reported, perhaps due to socioeconomic and tropical conditions in this region of Brazil, and thus coincided with the HHV-6 infections. This study also highlights the difficulties of diagnosing a rash illness on clinical grounds alone.
In March 1999, a large community outbreak of Escherichia coli O157 infection occurred in North Cumbria. A total of 114 individuals were reported to the Outbreak Control Team (OCT); 88 had laboratory confirmed E. coli O157. Twenty-eight (32%) of the confirmed cases were admitted to hospital, including three children (3·4%) with haemolytic uraemic syndrome. There were no deaths. A case-control study found that illness was strongly associated with drinking pasteurized milk from a local farm (P=<0·0001) on single variable analysis. Microbiological investigations at the farm revealed E. coli O157 phage type (PT) 21/28 VT 2 which was indistinguishable from the human isolates by pulsed field gel electrophoresis. At the time of occurrence this was the largest E. coli O157 outbreak in England and Wales and the first E. coli O157 PT 21/28 VT 2 outbreak associated with pasteurized milk. This outbreak highlights lessons to be learnt regarding on-farm pasteurization.
A study investigating the causes of rash diseases using systematic laboratory testing was conducted in Niterói, Rio de Janeiro, between January 1994 to April 1998. Sera from 327 patients were tested for evidence of anti-rubella virus, measles virus, human parvovirus B19 and dengue fever virus specific immunoglobulin IgM and anti-human herpes virus type 6 (HHV-6) IgG antibodies. A laboratory confirmed diagnosis was achieved in 71·3% of the cases investigated: dengue fever (33·0%), rubella (20·2%), parvovirus B19 (9·2%), measles (6·7%) and HHV-6 (2·1%). No diagnosis was established for 94 cases (28·7%). An outbreak of measles was detected during 1997, with a peak in September and October. All of the diseases studied here presented with clinical features similar to measles and classical symptoms were found in all measles confirmed cases. The large overlap of combinations of signs and symptoms seen in this study highlights the difficulties of diagnosing a rash illness on clinical grounds alone.
Nine isolates from pigs persistently infected with a recent Italian isolate of swine vesicular disease (SVD) virus, ITL/9/93, were collected sequentially over 121 days and were characterized antigenically and biochemically. There was an accumulation of amino acid (aa) substitutions in the capsid proteins throughout the carrier state that could be correlated with alterations in antigenicity in virus isolates collected late stage in infection. The aa substitutions detected mainly occurred in VP1 and antigenic changes were detected in late isolates both at antigenic site 1, resulting in loss of binding of Mab 4GO7, and at a closely located site which has not yet been named, recognized by Mab C29. In further experiments groups of pigs were exposed to a range of SVD viruses, but no virus was isolated beyond 16 days post infection (dpi) nor viral RNA detected beyond 42 dpi. Attempts to transfer infection to sentinel pigs introduced some time after initial infection of the original pigs were largely unsuccessful. The carrier state was established in only one out of five experimental infections of pigs with SVD virus and can therefore be considered a rare sequel to infection with SVD virus and is of limited significance in the epidemiology of the disease.
Partial nucleotide sequence at the 3′ end of 1D (VP1-encoding) gene of 90 foot-and-mouth
disease virus type O isolates recovered from field outbreaks in India between 1993–9 were
determined. The sequences were compared with each other and reference viruses. The published
sequences of 15 type O isolates recovered from different parts of Asia and one isolate (O1BFS)
from Europe and one from Egypt (O1/Sharquia/Egypt/72) were also included in the analysis
for comparison. On the basis of phylogenetic analysis the viruses could be grouped into four
distinct genotypes (genotypes I–IV). All 90 isolates from India were genotype-I, as were the
reference isolates from Bangladesh, China, Egypt, Iran, Saudi Arabia, Syria and Turkey.
Genotype-I isolates were further subdivided into 16 sub-genotypes. The Indian isolates were
found to be extremely heterogeneous in nature and clustered into 12 different genetic groups.
In genotype-I, the nucleotide sequence difference seen between the isolates was 0–11·6%, while
among the Indian isolates it is 0–8·8%. Viruses of similar genetic groups are circulating in
India, Bangladesh and countries of the Middle East. Genotype-II and -III are represented by
isolates from Lebanon (O1/South Lebanon) and Europe (O1-BFS), respectively. Genotype-IV
is formed by isolates from China, Hong Kong and Taiwan. The present study reveals the
occurrence of viruses belonging to multiple genetic groups over a short period of time and
persistence of single genetic group in the same geographical area over several years. This is
consistent with the endemic nature of the disease in the country.